Hepatitis C virus (HCV) is one of the major causes of liver inflammation. The aim of this study was to investigate the associations of T-cell immunoglobulin and mucin domain-3 (Tim-3) polymorphisms and the alternate reading frame protein (F protein) with the outcomes of HCV infection. Three single-nucleotide polymorphisms (SNPs; rs10053538, rs12186731, and rs13170556) of Tim-3 were genotyped in this study, which included 203 healthy controls, 558 hepatitis C anti-F-positive patients, and 163 hepatitis C anti-F-negative patients. The results revealed that the rs12186731 CT and rs13170556 TC and CC genotypes were significantly less frequent in the anti-F-positive patients [odds ratio (OR) = 0.54, 95 % confidence interval (CI) = 0.35–0.83, p = 0.005; OR = 0.26, 95 % CI = 0.18–0.39, p < 0.001; and OR = 0.19, 95 % CI = 0.10–0.35, p < 0.001, respectively), and the rs13170556 TC genotype was more frequent in the chronic HCV (CHC) patients (OR = 1.70, 95 % CI = 1.20–2.40, p = 0.002). The combined analysis of the rs12186731 CT and rs13170556 TC/CC genotypes revealed a locus-dosage protective effect in the anti-F-positive patients (OR = 0.22, 95 % CI = 0.14–0.33, ptrend < 0.001). Stratified analyses revealed that the frequencies of the rs12186731 (CT + TT) genotypes were significantly lower in the older (OR = 0.31, 95 % CI = 0.15–0.65, p = 0.002) and female (OR = 0.30, 95 % CI = 0.17–0.52, p < 0.001) subgroups, and rs13170556 (TC + CC) genotypes exhibited the same effect in all subgroups (all p < 0.001) in the anti-F antibody generations. Moreover, the rs13170556 (TC + CC) genotypes were significantly more frequent in the younger (OR = 1.86, 95 % CI = 1.18–2.94, p = 0.007) and female (OR = 2.38, 95 % CI = 1.48–3.83, p < 0.001) subgroups of CHC patients. These findings suggest that the rs12186731 CT and rs13170556 TC/CC genotypes of Tim-3 provide potential protective effects with the F protein in the outcomes of HCV infection and that these effects are related to sex and age.
HBsAg Seroclearance Alternate Reading Frame Protein
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Compliance with ethical standards
This study was funded by grants from the National Natural Science Foundation of China (grant nos. 81573213 and 81172724), the Natural Science Foundation of Jiangsu Province, China (grant nos. BK20151089 and BL2013021), and the Tian Qing Liver Disease Research Fund of the Chinese Hepatitis Foundation (grant no. CFHPC20132071).
Conflict of interest
The authors declare that they have no conflicts of interest.
All procedures performed in the studies involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in this study.
National Natural Science Foundation of China (CN) (81573213); Xiaozhao Deng.
National Natural Science Foundation of China (CN) (81172724); Xiaozhao Deng.
Natural Science Foundation of Jiangsu Province, China (BK20151089); Xiaozhao Deng.
Natural Science Foundation of Jiangsu Province, China (BL2013021); not applicable.
Tian Qing Liver Disease Research Fund of Chinese Hepatitis Foundation (CFHPC20132071); Longfeng Jiang.
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